C-MYB AND V-MYB ARE DIFFERENTIALLY PHOSPHORYLATED BY P42MAPK IN-VITRO

The product of the c-myb proto-oncogene is a highly conserved transcri ption factor that has been shown to function as both a transactivator and repressor. The v-myb oncogenes of E26 leukemia virus and avian mye loblastosis virus (AMV) encode proteins truncated at both the amino an d carboxy termini, deleting portions of the DNA-binding and negative r egulatory domains present in c-Myb. Similar truncations of c-Myb alter its function, suggesting that the viral proteins lack important regul atory sequences. Interestingly, eight potential sites of phosphorylati on by proline-directed protein kinases conserved between the avian, mu rine and human Myb proteins are clustered in or near the negative regu latory domain of c-Myb. The majority of these sites are deleted in bot h the E26 and AMV viral proteins. In this paper we show that one proli ne-directed protein kinase, p42mapk, phosphorylates bacterially synthe sized avian and murine c-Myb but not AMV v-Myb in vitro. We find that p42mapk phosphorylates c-Myb on serine and threonine, but not on tyros ine. Furthermore, deletion analysis indicates that the sites of phosph orylation map to the C-terminal negative regulatory domain. We specula te that the inability of v-Myb to be phosphorylated by p42mapk may con tribute to its oncogenic properties.